The objectives of the proposed research are to continue our investigation of the anti-convulsant properties of cannabidiol (CBD) and its mechanism of action, and to extend our study of the potentially toxic seizure properties of delta 9-tetrahydrocannabinol (delta 9-THC). The purpose of the delta 9-THC study is to determine the extent to which its seizure activity can augment that produced by other causes. Experimentally, the delta 9-THC effect will be assessed on the susceptibility to convulsions induced by a variety of convulsant drugs and electroshock tests, and on the seizure activity of a focal type of epilepsy. The effects of delta 9-THC on these test systems will be defined in both acutely and chronically treated animals. In addition, the influence of chronic delta 9-THC or CBD treatment on the development of electrically or pharmacologically induced kindling will be investigated to determine whether delta 9-THC's seizure activity promotes kindling and whether CBD's anticonvulsant activity retards kindling. Similarly, the chronic treatment effects on these two drugs on a focal type of epilepsy will also be studied. Finally, the electrophysiological mechanisms of the excitatory and anticonvulsant effects of these two drugs will be investigated at a synaptic level. The cat spinal motoneuron will be used to describe the cannabinoid effects on mono- and polysynaptic responses, on presynaptic and disynaptic and recurrent inhibition, on synaptic depression, facilitation and recovery time, on inhibitory postsynaptic potentials (IPSPs) and excitatory postsynaptic potentials (EPSPs), on the IPSP reversal potential, on the action potential threshold of the motoneuron and on postsynaptic membrane resistance, as well as on afferent nerve action potentials. The rationale for these studies is that the cannabinoids probably exert their effects at the synapse, and a definition of these effects will enhance an understanding of both the toxic potential of marihuana vis-a-vis its delta 9-THC content and the clinical potential of CBD as an antiepileptic.